EC Grants Brentuximab Vedotin New Indication for Hodgkin Lymphoma

The European Commission (EC) has approved brentuximab vedotin (Adcetris) for use as a consolidation therapy following autologous stem cell transplantation (ASCT) in patients with CD30-positive Hodgkin lymphoma at risk of relapse or progression.

The approval was based on the phase III AETHERA trial, in which brentuximab vedotin reduced the risk of disease progression by 43% compared with placebo. The median progression-free survival (PFS) with brentuximab vedotin was 42.9 months versus 24.1 months with placebo (HR, 0.57; 95% CI, 0.40-0.81; P = .001).

Along with the expanded indication, the EC also extended the existing conditional marketing approvals for brentuximab vedotin in Europe. The EC decision, which follows a recent positive opinion issued by the EMA’s Committee for Medicinal Products for Human Use (CHMP), means that brentuximab vedotin is now approved for these indications in the European Union, Norway, Liechtenstein, and Iceland.

“Relapse is a devastating event for patients with Hodgkin lymphoma and their families. Not only is the emotional impact significant, but the challenge of treating their disease becomes much greater,” Andreas Engert, MD, University Hospital of Cologne, Germany, said in a statement. “For the first time, physicians in the European Union will now have a well-tolerated and effective treatment option that may be used immediately posttransplant to reduce the risk of relapse for Hodgkin lymphoma patients at increased risk.”

In the phase III AETHERA study, 329 patients were randomized to receive brentuximab vedotin (n = 165) or placebo (n = 164). Brentuximab vedotin was administered at 1.8 mg/kg IV every 3 weeks for a median of 15 cycles. A majority (60%) of patients treated in the study were refractory to frontline therapy. All patients were required to have obtained a complete remission (CR), partial remission (PR), or stable disease (SD) to salvage therapy prior to ASCT.

The median age of patients enrolled in the trial was 32 years. The median number of prior therapies was 2 (range, 2-8), with 47% of patients receiving >2 prior therapies. Overall, 42% of patients had experienced a prior CR with salvage therapy, a PR for 34%, and SD in 24%. The primary endpoint of the study was PFS, with secondary endpoints focused on overall survival (OS) and safety.

The 2-year PFS rate for patients treated with brentuximab vedotin following ASCT was 54%. The hazard ratio for PFS was consistently below 1.00 across all subgroups analyzed in the study, including patients with primary refractory disease. For patients with primary-refractory disease, the 2-year PFS rate was 60% with brentuximab vedotin compared with 42% for placebo.

The estimated 2-year OS rates with brentuximab vedotin and placebo were both 88%. This endpoint was potentially confounded by crossover, as 85% of patients in the placebo arm received brentuximab vedotin when the trial was unblinded in September 2014.

The most common all-grade adverse events with brentuximab vedotin versus placebo were peripheral sensory neuropathy (56% vs 16%) and neutropenia (35% vs 12%). A majority (85%) of patients who experienced peripheral neuropathy with brentuximab vedotin had resolution of this adverse event within a median of 23.4 months. The primary cause of treatment discontinuation was progression.

“The AETHERA phase III data further reinforces the role of Adcetris in earlier line treatment and may offer new hope for posttransplant Hodgkin lymphoma patients,” Dirk Huebner, MD, executive medical director of the Oncology Therapeutic Area Unit at Takeda, which is codeveloping the antibody-drug conjugate with Seattle Genetics, said in a statement. “The European Commission decision is a significant milestone for patients who are at risk of relapse following stem-cell transplant as Adcetris provides a treatment where none currently exists.”

The European Commission previously granted brentuximab vedotin marketing authorization for two indications. The first was for patients with relapsed/refractory CD30-positive Hodgkin lymphoma after ASCT, or after at least 2 prior therapies in patients not eligible for ASCT or multiagent chemotherapy. The second was for patients with relapsed/refractory systemic anaplastic large cell lymphoma (sALCL). Following these approvals, the EC later approved a Type II variation to add data on the retreatment of patients with Hodgkin lymphoma or sALCL who relapse after previously responding to brentuximab vedotin.